Treatment Dilemma Research Articles

Single tertiary cancer center experience on the management of pT3b prostate cancer after robotic-assisted laparoscopic prostatectomy.

Pathological involvement of the seminal vesicle poses a treatment dilemma following robotic prostatectomy. Margin status plays an important role in deciding further management. A wide range of treatment options are available, including active monitoring, adjuvant radiotherapy, salvage radiotherapy, and occasionally androgen deprivation therapy. Patients undergoing postoperative radiotherapy tend to have higher risk of urinary and bowel morbidities. The recent RADICALS-RT concluded that adjuvant radiotherapy did not have any benefit compared with salvage radiotherapy. We aim to audit the incidence, margin status, and management of T3b cancer cases at our center. A retrospective analysis was conducted of all patients diagnosed with pathological T3b (pT3b) prostate cancer following robotic-assisted laparoscopic prostatectomy from January 2012 to July 2020. Preoperative parameters analyzed included prostate-specific antigen (PSA), T stage, and age. A chi-square test and 2-tailed t test were used to determine the relationship between categorical and continuous variables, respectively. Kaplan-Meier survival curves were generated to assess overall survival in patients with pT3b prostate cancer and used to compare unadjusted progression-free survival among those who underwent adjuvant and salvage radiotherapy. A total of 83 (5%) of 1665 patients who underwent robotic prostatectomy were diagnosed with pT3b prostate cancer between January 2012 and July 2020. Among these, 36 patients (44%) did not receive any radiotherapy during follow-up, compared with 26 patients (31%) who received adjuvant radiotherapy and 21 (25%) who received salvage radiotherapy. The median age of our cohort was 64 (SD, 6.4) years. Mean PSA at presentation was 12.7 μg/L. Positive margins were seen in 36 patients (43%); however, there was no statistically significant difference between treatment groups (p = 0.49). The median overall survival was 96%. There was no significant difference between the adjuvant and salvage groups in terms of biochemical progression-free survival (p = 0.66). Five-year biochemical progression-free survival was 94% for those in the adjuvant radiotherapy group and 97% for those in the salvage radiotherapy group. Our audit corroborates with the recently concluded RADICALS-RT study, although we had fewer patients with positive margins. Radiotherapy can be avoided in patients with T3b prostate cancer, even if margin is positive, until there is definitive evidence of PSA recurrence. In keeping with the conclusion of RADICALS-RT, salvage radiotherapy may be preferable to adjuvant radiotherapy.

Antibody-mediated rejection: prevention, monitoring and treatment dilemmas.

Purpose of reviewAntibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk factor for AMR and graft loss. However, not all donor-specific antibodies are pathogenic. AMR treatment is heterogeneous due to the lack of robust trials to support clinical decisions. This review provides an overview and comments on practical but relevant dilemmas physicians experience in managing kidney transplant recipients with AMR.Recent findingsActive AMR with donor-specific antibodies may be treated with plasmapheresis, intravenous immunoglobulin and corticosteroids with additional therapies considered on a case-by-case basis. On the contrary, no treatment has been shown to be effective against chronic active AMR. Various biomarkers and prediction models to assess the individual risk of graft failure and response to rejection treatment show promise.SummaryThe ability to personalize management for a given kidney transplant recipient and identify treatments that will improve their long-term outcome remains a critical unmet need. Earlier identification of AMR with noninvasive biomarkers and prediction models to assess the individual risk of graft failure should be considered. Enrolling patients with AMR in clinical trials to assess novel therapeutic agents is highly encouraged.

Long-term survival in a patient with extensive-stage small cell lung cancer treated with multiple courses of salvage stereotactic radiation after whole brain radiotherapy: A case report.

Intracranial recurrence following initial cranial irradiation for extensive-stage small cell lung cancer (ES-SCLC) can often be a treatment dilemma given the aggressive nature of the disease, the overall poor prognosis and concerns regarding re-treatment toxicity. The present report describes the case of a 62-year-old man diagnosed with ES-SCLC and synchronous brain metastases who initially underwent whole brain radiotherapy, chemotherapy and consolidative thoracic radiotherapy. The patient was found to have a solitary intracranial recurrence at both 3.5 and 6 years after his diagnosis. On both occasions, the patient received salvage stereotactic radiation, 30 Gy in 5 fractions, and continues to remain functionally independent. Overall, the present case demonstrates that with the appropriate patient selection, aggressive local salvage of recurrent intracranial ES-SCLC with stereotactic radiation can yield excellent and durable clinical outcomes.

Identifying RBBP7 as a Promising Diagnostic Biomarker for BK Virus-Associated Nephropathy

BK virus-associated nephropathy (BKVN) remains a major infectious complication due to powerful immunosuppression in kidney transplant recipients, and its histologic appearance can mimic rejection, leading to diagnostic and treatment dilemmas thus molecular diagnostic methods would be beneficial. We collected gene expression profiles of 169 kidney biopsies taken from BKVN, rejection, and stable functioning allografts, based on single sample gene set enrichment analysis and random forest algorithm, and three hallmark activities associated with DNA damage and proliferation were found to be relatively specific in BKVN. Subsequently, weighted gene co-expression network analysis and support vector machines (SVM) algorithm identified RBBP7 as a robust and promising biomarker with high accuracy in both training and validation cohorts (AUC =0.938, 0.977, respectively). Besides, potential drugs for BKVN treatment such as mepacrine were discovered, which may contribute to targeted antiviral therapy and effective patient management rather than simply reducing the doses of immunosuppressive agents in clinical practice. RBBP7 (retinoblastoma binding protein 7) serves as component of serval complexes that regulate chromatin metabolism and functions in affecting DNA replication and controlling cell proliferation. In this research, upregulation of RBBP7 was found to be associated with the higher infiltration of CD8 naïve T, iTreg, and neutrophil cells and the lower amounts of Th1, central memory T, NKT, CD8 T, and dendritic cells. Moreover, the infiltration of Th1, Th17, and NKT cells was steadily different between BKVN and rejection allografts through immune cell assessment. In conclusion, we identified and verified RBBP7 as a molecular biomarker for BKVN diagnosis, which demonstrated great distinguishing ability with allograft rejection and would support clinical decision-making.

Targeted Arginine Metabolism Therapy: A Dilemma in Glioma Treatment.

Efforts in the treatment of glioma which is the most common primary malignant tumor of the central nervous system, have not shown satisfactory results despite a comprehensive treatment model that combines various treatment methods, including immunotherapy. Cellular metabolism is a determinant of the viability and function of cancer cells as well as immune cells, and the interplay of immune regulation and metabolic reprogramming in tumors has become an active area of research in recent years. From the perspective of metabolism and immunity in the glioma microenvironment, we elaborated on arginine metabolic reprogramming in glioma cells, which leads to a decrease in arginine levels in the tumor microenvironment. Reduced arginine availability significantly inhibits the proliferation, activation, and function of T cells, thereby promoting the establishment of an immunosuppressive microenvironment. Therefore, replenishment of arginine levels to enhance the anti-tumor activity of T cells is a promising strategy for the treatment of glioma. However, due to the lack of expression of argininosuccinate synthase, gliomas are unable to synthesize arginine; thus, they are highly dependent on the availability of arginine in the extracellular environment. This metabolic weakness of glioma has been utilized by researchers to develop arginine deprivation therapy, which ‘starves’ tumor cells by consuming large amounts of arginine in circulation. Although it has shown good results, this treatment modality that targets arginine metabolism in glioma is controversial. Exploiting a suitable strategy that can not only enhance the antitumor immune response, but also “starve” tumor cells by regulating arginine metabolism to cure glioma will be promising.

Effect of Ultraviolet-c (UVc) light and ozone on the survival of Mycobacterium abscessus complex organisms associated with cystic fibrosis.

Members of the Mycobacterium abscessus complex have now emerged as clinically significant respiratory pathogens in people with cystic fibrosis (CF), potentially leading to increased disease severity, antibiotic treatment, and persistence dilemmas. Many of these species are resistant to disinfectants and biocides commonly used to clean and disinfect the hospital environment, thus necessitating the need to examine innovative ways to eliminate these organisms from such environments. It was, therefore, the aim of this study to examine the individual effect of ultraviolet-c (UVc) light (λ = 254 nm) and ozone (O3) on the growth of the M. abscessus complex organisms, as well as on seven other clinically significant CF pathogens, including Achromobacter spp., Burkholderia gladioli, Burkholderia cenocepacia, Burkholderia multivorans, Pseudomonas aeruginosa, Staphylococcus aureus, and Stenotrophomonas maltophilia. Bacterial isolates (n = 46), including M. abscessus complex (n = 6) (M. abscessus subsp abscessus [n = 2], M. abscessus subsp. bolletii [n = 2], M. abscessus subsp. massiliense [n = 2]), and other CF pathogens (n = 40) including Achromobacter spp., B. gladioli, B. cenocepacia, B. multivorans, P. aeruginosa, S. aureus, and S. maltophilia, were exposed for 1 h to UVc light (254 nm), as well as to ozone (O3; 26 ppm). UVc light inactivated all M. abscessus complex organisms (n = 6), as well as the 40 isolates from the other genera and species. No bacterial species tested was able to survive the UVc treatment. O3 was unable to inactivate all isolates of M. abscessus subsp. abscessus (n = 2), M. abscessus subsp. bolletii (n = 2), and one isolate of M. abscessus subsp. massiliense, but killed one strain of M. abscessus subsp. massiliense. Overall, O3 inactivated only 20% of total isolates, allowing the posttreatment growth of the remaining 80% of isolates. There was no difference in the growth dynamic of P. aeruginosa from the environmental waters which had received O3 treatment and the control (untreated with O3). Bacterial growth, while occurring post-O3 treatment, was not as prolific in all remaining organisms, as in the untreated controls, demonstrating some but limited antibacterial effect. From the data presented by this study, UVc light at 254 nm was effective at eliminating all organisms examined, including members of the M. abscessus complex. Given the refractory nature of these organisms against conventional wet chemical disinfection, UVc potentially offers a physical method to control and eliminate the survival of these organisms on health-care surfaces and fomites. For many CF species examined in this study, these data represent the first reports of the organisms susceptibility to UVc light. Further work is now required to establish time/distance parameters incorporated into newly designed innovative devices, to allow disinfection protocols to be optimized, and delivered to exploit this vulnerability with these nontuberculous mycobacterial organisms, as well as with the other bacterial species examined.

A Case Series on GeneXpert Negative Tuberculous Mastitis and the Effect of Anti-tuberculous Treatment

Background: Breast tuberculosis is significant due to its rare occurrence and dilemma in prospective treatment and differentiation from neoplastic lesions. Tuberculosis of the breast usually affects women from Asia, most commonly, the Indian subcontinent and Africa. Tuberculous mastitis has a wide range of clinical presentation, radiological features, and even microbiological presentation. Materials and Method: A prospective study was conducted over 6 months. 40 female patients with varied presentations correlating to tuberculous mastitis with a lump in the breast for a particular period of time were included in the study. Results: The patients’ ages varied from 20 to 45 years. After routine investigations, the patients went in for incision and drainage or incisional biopsy or both and postoperatively their histopathological reports revealed granulomatous breast disease (tuberculous mastitis) with negative GeneXpert (CB-NAAT). Patients were started on an anti-tubercular treatment regimen and showed a progressive decrease in symptomatology. Conclusion: Granulomatous breast abscess/ tuberculous breast abscess has a varied presentation and no fixed treatment regime. Anti-tuberculous drugs in such patients proved to be efficacious in symptomatic relief with prevention of recurrence/ fistula formation.

Aortic Thrombosis and Ischemic Stroke With Hemorrhagic Conversion in a Patient With Remote COVID-19 Infection: A Treatment Dilemma

Coronavirus disease 2019 (COVID-19) is primarily known to affect the lungs; however, several studies indicate that it can be a multisystem disease. There is documentation detailing different sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients affected with this virus have been seen to develop a hypercoagulable state leading to systemic thrombosis in some cases or embolism leading to catastrophic outcomes in others. Data regarding anticoagulation in these patients is limited. Further research needs to be carried out for management and prophylaxis for patients with COVID-19 at risk of aortic thrombosis. We present a case of a middle-aged man with multiple comorbidities and remote COVID-19 infection who came to the emergency room with signs and symptoms worrisome for a cerebrovascular accident (CVA). Brain imaging revealed multiple cortical infarcts suggestive of a cardioembolic etiology. During his hospitalization, he underwent a transesophageal echocardiogram (TEE) that showed a 1x1 cm mobile thrombus in the distal descending aorta. Laboratory workup was negative for any hypercoagulable condition; it was thought that this patient might have a hypercoagulable state post-COVID-19 infection. After a thorough risk vs. benefit discussion, patient was started on apixaban. He remains alive and is doing well in a recent follow-up in our clinic.

Quadruple Primary Malignancy of the Scalp, Colon, and Prostate in a Single Patient: A Unique Case Report and Review of Literature

Multiple primary malignancies are rare but early detection can be achieved with the advent of advanced imaging techniques. Diagnosis of all synchronous malignancy is vital for planning and favorable outcome. In this study, we present a case of synchronous triple primary malignancy consisting of squamous carcinoma scalp, adenocarcinoma prostate, and adenocarcinoma ascending colon with history of sigmoid colon cancer 11 years back. There were 12 possible treatment options and three alternative treatment sequences. Multidisciplinary tumor board team decided to begin the treatment with hormonal therapy (Enzalutamide/Leuprolide) for advanced metastatic prostate cancers. This was followed by simultaneous surgery consisting of wide excision of the right scalp lesion and right hemicolectomy. After a year of follow-up, patient remained disease progression free. This is the first quadruple malignancy case described in literature with the combination of scalp, prostate, and colon cancers as triple synchronous malignancy. Each cancer had its own diagnostic and treatment dilemma. Collectively, sequence of management of each cancer was also a predicament. Multidisciplinary management plays a pivotal role in the successful management of synchronous malignant tumors.

Guidance for family about comfort care in dementia: a comparison of an educational booklet adopted in six jurisdictions over a 15 year timespan

BackgroundTo support family caregivers of people with dementia in end-of-life decision making, a family booklet on comfort care has been adapted and adopted by several European jurisdictions since the original publication in Canada in 2005.MethodsWe analyzed and compared the adaptations to the family booklets used in Canada, the Czech Republic, Italy, the Netherlands, the UK and Ireland that were made up to 2021. Qualitative content analysis was used to create a typology of changes to the original booklet. Interviews with the teams that adapted the booklets contributed to methodological triangulation. Further, using an established framework, we assessed whether the contents of the booklets addressed all domains relevant to optimal palliative dementia care.ResultsThe booklets differed in the types of treatment addressed, in particular tube feeding, euthanasia, and spiritual care. There was also variability in the extent to which medical details were provided, an emphasis on previously expressed wishes in medical decision making, addressing of treatment dilemmas at the end of life, the tone of the messages (indirect or explicit) and the discussion of prognosis (as more or less positive), and the involvement of various healthcare professionals and family caregivers in care. All booklets addressed all domains of palliative dementia care.ConclusionsWe identified core elements in providing information on end-of-life care to family caregivers of people with dementia as related to optimal palliative care in dementia. Additionally, local adaptations and updates are required to account for socio-cultural, clinical, and legal differences which may also change over time. These results may inform development of educational and advance care planning materials for different contexts.

An unusual cause of pneumomediastinum and acute respiratory distress syndrome

BackgroundProgressive acute respiratory failure with Mycobacterium tuberculosis (TB) in immunocompetent individuals is rare, and if detected early, diagnosis and treatment dilemmas can be limited. We report here a unique case of respiratory failure due to tubercular spontaneous pneumomediastinum complicated by acute respiratory distress syndrome (ARDS).Case presentationA 24-year-old male of low socioeconomic background presented with shortness of breath, dry cough, and fever for 7 days, which was accompanied by weight loss and a reduced appetite. The patient had tachypnea and hypoxemia (SpO2 = 86%). The patient’s condition deteriorated (SpO2 = 72% with 12 L min−1of O2 delivered using a non-rebreather mask), and he was intubated using a lung-protective approach with a tidal volume of 350 mL (6 mL kg−1), positive end-expiratory pressure (PEEP) of 5 cm H2O, RR of 20 cycles/min, a flow rate of 35 L min−1, and FiO2 of 0.6. High-resolution computer tomography of the thorax showed multilobar consolidation, pneumomediastinum, and extensive subcutaneous emphysema with left-sided pneumothorax. Subsequently, a left-sided tube thoracostomy was carried out. The PaO2/FiO2 (P/F) ratio immediately after intubation was 130 and rose to 170 post-thoracostomy, which was suggestive of moderate ARDS. Bacterial and fungal colonies detected from the blood and endotracheal aspirate were normal. However, for the endotracheal aspirate, the cartridge-based nucleic acid amplification test (CBNAAT) detected TB with no rifampicin resistance. The patient was started on anti-tubercular therapy (ATT). Despite ATT, the patient developed circulatory shock and died after 4 days.ConclusionsIn young patients with acute spontaneous pneumomediastinum and ARDS, TB infection should be considered during initial diagnostics. This consideration may lead to timely treatments and improved patient survival.

How longitudinal observational studies can guide screening strategy for rare diseases.

Newborn screening (NBS) is an important secondary prevention program, aiming to shift the paradigm of medicine to the pre-clinical stage of a disease. Starting more than 50 years ago, technical advances, such as tandem mass spectrometry (MS/MS), paved the way to a continuous extension of NBS programs. However, formal evidence of the long-term clinical benefits in large cohorts and cost-effectiveness of extended NBS programs is still scarce. Although published studies confirmed important benefits of NBS programs, it also unraveled a significant number of limitations. These include an incompletely understood natural history and phenotypic diversity of some screened diseases, unreliable early and precise prediction of individual disease severity, uncertainty about case definition, risk stratification, and indication to treat, resulting in a diagnostic and treatment dilemma in individuals with ambiguous screening and confirmatory test results. Interoperable patient registries are multi-purpose tools that could help to close the current knowledge gaps and to inform further optimization of NBS strategy. Standing at the edge of introducing high throughput genetic technologies to NBS programs with the opportunity to massively extend NBS programs and with the risk of aggravating current limitations of NBS programs, it seems overdue to include mandatory long-term follow-up of NBS cohorts into the list of screening principles and to build an international collaborative framework that enables data collection and exchange in a protected environment, integrating the perspectives of patients, families, and the society.

The Concomitant Incidence of Multiple Sclerosis and Primary CNS Tumors Leading to Treatment Dilemma. (P16-9.005)

The Concomitant Incidence of Multiple Sclerosis and Primary CNS Tumors Leading to Treatment Dilemma. (P16-9.005)

Avelumab in unresectable/metastatic, progressive, grade 2–3 neuroendocrine neoplasms (NENs): Combined results from NET-001 and NET-002 trials

BackgroundHigher grade neuroendocrine neoplasm (NENs) continues to pose a treatment dilemma, with the optimal treatment undefined. Although immunotherapy has revolutionised the treatment of many cancers, its role in NENs remains unclear. We aimed to investigate the efficacy and safety of avelumab, a PD-L1-directed antibody, in patients with advanced unresectable/metastatic higher grade NENs. MethodsNET001 and NET002 are phase II studies investigating avelumab (NCT03278405 and NCT03278379). Eligible patients had unresectable and/or metastatic WHO G2-3 NENs from a gastroenteropancreatic (GEP) source or a bronchial primary (excluding typical carcinoid) and 0–2 prior lines of systemic therapy (excluding SSAs). Patients were treated with avelumab 10 mg/kg intravenously every two weeks for 26 cycles. NET001 investigated G3 poorly differentiated GEP neuroendocrine carcinomas (NECs) and bronchial small/large cell NEC, whereas NET002 investigated G2-3 well-differentiated GEPNETs and bronchial atypical carcinoids. The primary endpoint in both trials was overall response rate (ORR) by RECIST v1.1; secondary endpoints included progression-free survival, overall survival, disease control rate at six months and toxicity. ResultsTwenty-seven patients were enrolled (21 GEP, 6 lung; 10 in NET-001, 17 in NET-002); median age 64 (range 37–80), 30% ECOG PS 1–2 and 78% received 1+ lines of prior therapy. The median Ki-67 index was 35% (range 10–100). Twelve of the twenty-seven patients had died at the time of data lock. The median time on treatment was 85 days (seven cycles). No objective responses were observed. Stable disease was achieved in 33% of patients, and the disease control rate at 6 mo was 21%. The median PFS was 3.3 months (range 1.2–24.6), and the median OS was 14.2 months. Treatment-related adverse events (all grades) occurred in 58% of patients. Three patients had treatment-related grade 3–4 AEs leading to treatment discontinuation (immune-related hepatitis n = 2 and infusion-related reaction n = 1). ConclusionSingle-agent PD-L1 blockade with avelumab showed limited antitumour activity in patients with G2-3 NENs. Correlative studies are underway. Further studies are needed to explore the role of dual immunotherapy and other combinations in this population with few treatment alternatives.

Engineering Islets From Stem Cells: The Optimal Solution for the Treatment of Diabetes?

Diabetes is a metabolic disease characterized by insulin deficiency. Bioengineering of stem cells with the aim to restore insulin production and glucose regulation has the potential to cure diabetic patients. In this review, we focus on the recent developments for bioengineering of induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and pancreatic progenitor cells in view of generating insulin producing and glucose regulating cells for β-cell replacement therapies. Recent clinical trials using islet cells derived from stem cells have been initiated for the transplantation into diabetic patients, with crucial bottlenecks of tumorigenesis, post-transplant survival, genetic instability, and immunogenicity that should be further optimized. As a new approach given high expectations, bioengineered islets from stem cells occupies considerable potential for the future clinical application and addressing the treatment dilemma of diabetes.

Patient and pathological predictors of management strategy for malignant polyps following polypectomy: a systematic review and meta-analysis

PurposeMalignant polyps present a treatment dilemma for clinicians and patients. This meta-analysis sought to identify the factors that predicted the management strategy for patients diagnosed with a malignant polyp.MethodsA literature search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Collaboration prognostic studies guidelines. Reports from 1985 onwards were included, data on patient and pathological factors were extracted and random effects meta-analysis models were used.ResultsFifteen studies were included. Seven studies evaluated lymphovascular invasion (LVI). The odds of surgery were significantly higher in malignant polyps with LVI (OR 2.20, 95% CI 1.36–3.55). Ten studies revealed the odds of surgery were significantly higher with positive polypectomy margins (OR 8.09, 95% CI 4.88–13.40). Tumour differentiation was compared in eight studies. There were significantly lower odds of surgery in malignant polyps with well/moderate differentiation compared with poor differentiation (OR 0.31, 95% CI 0.21–0.46). There were non-significant trends favouring surgical resection in younger patients, males and Haggitt 4/Kikuchi Sm3 lesions. There was considerable heterogeneity in the meta-analyses for the variables age, gender, polyp morphology and Haggitt/Kikuchi level (I2 > 75%).ConclusionThis meta-analysis has demonstrated that LVI, positive polypectomy resection margins, and poor tumour differentiation significantly predict malignant polypectomy patients who underwent subsequent surgery. Age and gender were important factors predicting management, but not consistently across studies, whilst polyp morphology and Haggitt/Kikuchi levels did not significantly predict the management strategy. Further research may assist in understanding the management preferences.

Endovascular Treatment and Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability or Dementia: A Scientific Statement From the American Heart Association/American Stroke Association.

Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.

Concomitant Pulmonary Tuberculosis and Invasive Aspergillosis Infection in an Immunocompetent Host.

Pulmonary tuberculosis (TB) is a common infection in developing countries and is associated with low socioeconomic status. It is considered a serious infection due it its long-term sequelae. Post-TB lung disease decreases life expectancy and increases the risk of recurrent TB infection. It also significantly increases the risk of other bacterial and fungal infections. Aspergillosis develops in the cavitary lesions of TB, worsening them and resulting in a deteriorating clinical situation. Concomitant pulmonary TB (PTB) and invasive aspergillosis is uncommon, particularly in the absence of factors that suppress the immune system. In this report, we describe the case of a healthy young adult without previous structural lung damage who presented with primary PTB and acute invasive aspergillosis infection, discuss the treatment dilemma and provide a literature review.LEARNING POINTSAspergillosis can mimic tuberculosis (TB) infection.Concomitant pulmonary TB and invasive aspergillosis is uncommon.The co-administration of antifungal and anti-TB medications presents significant therapeutic challenges.

Gastrointestinal symptoms of Parkinson’s disease: A systematic review from pathogenesis to management

The identification of Parkinson’s disease (PD) is mainly dependent on motor symptoms, while the non-motor symptoms exist even decades ahead of the PD diagnosis. According to Braak’s hypothesis, the enteric plexus is the first affected site during the pathological development of PD, and gastrointestinal (GI) symptoms appear during the onset of the disease. Although GI symptoms decrease the life quality of patients with PD, there is often less focus on GI symptoms compared with motor symptoms. In this review, we summarize the pathophysiological basis, clinical manifestation, diagnosis, and treatment of GI symptoms in patients with PD. We also discuss the treatment and research dilemmas, as well as the research direction in the near future.

Parietal Peritoneal Flap for Post-radiation Bladder Injury Repair.

Inadvertent bladder injuries during pelvic surgery are not uncommon. Repair of these cystotomies are generally easy. However, post-radiation, the urinary bladder becomes contracted, friable and difficult to heal. Injuries in this setting present a treatment dilemma especially when there is absence of viable native tissue such as omentum for tissue buttress. The authors report a case of parietal peritoneal flap for post-radiation bladder injury repair based on twigs from the inferiorepigastric vessels. This flap being easy to perform is believed to be a viable alternative to musculocutaneous flaps especially in the emergency setting.